Environmental risk assessment and human pharmaceuticals : limitations and future improvements

摘要: A cocktail of human pharmaceuticals contaminate surface waters worldwide in the ng-?gl-1 range. Adverse effects on non target organisms including endocrine disruption and alterations behaviour growth have been reported. All new require an environmental risk assessment (ERA) prior to market authorisation. The aims for this research were (1) assess limitations current ERA by comparing crude refined predicted concentrations (PECs) used ERAs with measured (MECs) from literature; (2) interview key people working field ecotoxicology order establish expert opinion area; (3) whether bioinformatics databases can be as a potential tool aid ecotoxicological tests use ERAs. The scientific literature was data mined concentration compared calculated PECs ten carbamazepine, diclofenac, 17? ethinyl estradiol, fluoxetine, gemfibrozil, ibuprofen, paracetamol, propranolol, tamoxifen Trimethoprim. An engagement exercise through questionnaire based interviews representatives regulatory bodies, water companies pharmaceutical well academics involved undertaken experts’ views management. genomic search drug homologues aquatic species selected undertaken. Molecular docking experiments two pharmaceuticals, diclofenac ibuprofen carried out Daphnia pulex, (water flea) Oncorhynchus mykiss (rainbow trout), Salmo salar (Atlantic salmon) Danio rerio (zebra fish). The may insufficient protect environment. underestimate MECs due simplicity calculations assumptions underpinning them. interviewees regarded exposure PEC calculation inaccurate recommended using modelling computer software solution. bulk had substantial deficiencies reporting data; setting standards peer reviewed journals make such more useful regulators policy makers. Interviewees felt that ecotoxicity would benefit intelligent approach incorporating mode action drug. results show protein targets are highly conserved some but not others. molecular indicate cyclooxygenase (COX 2) primary probably functional O.mykiss, S.salar D.rerio D.pulex. It appears indeed informing choice relevant chronic test endpoints directing sensitive selection. Such techniques might contribute appropriately targeted testing. 10 ngl-1 limit inappropriate mechanism trigger tests. analysis shows many existing regularly exceed assessment. system prioritisation is required need retrospective these medicines. This thesis provides original makes recommendations improvements. novel application utilizing has direct